Cystic fibrosis drug ups lung function by targeting cause
Over two decades ago, scientists discovered the mutation that causes cystic fibrosis (CF), the world’s most common hereditary lung disease. Now, a drug based on that finding is on the verge of finally helping patients.
The drug known as VX-770 targets the defective protein that causes certain CF cases and improves lung function. Last week, it passed a phase 3 clinical trial, announced the Cystic Fibrosis Foundation and Vertex Pharmaceuticals.
People with CF – that’s about 70,000 worldwide – develop mucus-filled lungs susceptible to infection. Few live past their 30s.
The trial involved 161 CF patients ages 12 and up who carry at least one copy of a specific CF mutation called G551D. Most participants had just 60% as much lung function as healthy people.
Compared to those on placebo, patients who took the drug:
- showed 10% improvement in lung function at 24 weeks, and sustained it for at least 48-weeks
- experienced 55% fewer pulmonary exacerbations (deterioration in symptoms)
- had improved weight gain, just over 6 pounds on average
- dropped to normal levels of sweat salt
"This is a champagne moment for the cystic fibrosis community," says trial investigator Stuart Elborn at Queen's University. As New Scientist explains:
No other treatments for cystic fibrosis have caused such dramatic improvements, probably because they alleviate symptoms rather than attacking the main cause – a defective protein in lung cells called the Cystic Fibrosis Transmembrane Regulator, or CFTR (pictured), discovered in 1989. VX-770 is the first of a new generation of drugs that attack and correct the protein.
In healthy people, CFTR proteins form channels in the surface membrane of lung and other cells; these channels shuttle chloride ions in and out of the cell.
VX-770 corrects the channels in CF patients who make a faulty form of the protein channel, which reaches the cell surface but is always closed. The drug opens the channels. "It means you have normal regulation of the airway surface liquid, so instead of accumulating mucus, it gets cleared away," Elborn explains.
However, only 4% of people with CF carry the G551D mutation – still, that’s thousands of people that VX-770 could help. About 1,800 different mutations in the CFTR gene have been implicated in the disease [Nature].
Vertex plans to submit a new drug application to the Food and Drug Administration in the second half of 2011. (Generally, the FDA takes between 6 and 12 months to review and rule on a drug application.) Results of the VX-770 trial of children ages 6 to 11 with the G551D mutation are expected in a few months.
The CF Foundation provided approximately $75 million for the development of VX-770. Vertex was founded the same year the CF gene was discovered. It hasn’t had a big commercial success yet and had a $2.5 billion net loss in the last 5 years [NYT].
ISI Group analyst Mark Schnoenebaum projected that annual sales of VX-770 could reach $600 million [WSJ]. Vertex's shares jumped 18% in premarket trading, Reuters reports, a level not seen since the end of November 2006.
Image: CFTR via wiki
This post was originally published on Smartplanet.com